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EC number: 226-378-9 | CAS number: 5384-21-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental study report.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Principles of method if other than guideline:
- The objective of the study was to assess the irritant and/or corrosive effects of test chemical on eye, when exposed by the ocular route in rabbits.
- GLP compliance:
- yes
Test material
- Reference substance name:
- 4,4'-methylenedi-2,6-xylenol
- EC Number:
- 226-378-9
- EC Name:
- 4,4'-methylenedi-2,6-xylenol
- Cas Number:
- 5384-21-4
- Molecular formula:
- C17H20O2
- IUPAC Name:
- 4-[(4-hydroxy-3,5-dimethylphenyl)methyl]-2,6-dimethylphenol
- Details on test material:
- - Name of test material (as cited in study report):4, 4’-methylenedi-2, 6-xylenol
- Molecular formula:C17H20O2
- Molecular weight:256.34 g/mol
- Substance type:organic
- Physical state:White Powder
- Lot/batch No.:Lot 1/03
- AI Content:99.79 %
- Storage condition of test material:The container was kept away from the heat and source of ignition and was tightly closed in a dry and cool place.
- Other:
Handling and Disposal
Safety precautions : Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the personnel.
Disposal : No test item was disposed during the conduct of the study.
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source:Procured from RABBI ROOF, Hyderabad.
- Age at study initiation:4.5 to 5.5 Months (Approximately)
- Weight at study initiation:Minimum: 1.746 kg and Maximum: 2.362 kg (Prior to Treatment)
- Health Status :Healthy young adult, Females were nulliparous and non pregnant.
- Housing:The animals were housed individually in stainless steel cages.
- Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle:All the cages and water bottles were changed minimum twice a week.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rabbit diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum.
- Acclimation period:Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No.-1) and 10 days (Animal No. 2 and 3) prior to the application of the test item.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.50 °C and Maximum: 22.20 °C
- Humidity (%):Minimum: 41.20 % and Maximum: 59.20 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit):100 mg
- Concentration (if solution):N/A
VEHICLE
- Amount(s) applied (volume or weight with unit):N/A
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A - Duration of treatment / exposure:
- 24 hrs
- Observation period (in vivo):
- All the animals were observed at 1, 24, 48 and 72 hours after instillation of test item.
- Number of animals or in vitro replicates:
- 3 female rabbits
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done):The treated eye of rabbit was washed with normal saline.
- Time after start of exposure:24 hours
SCORING SYSTEM:Draize Method
TOOL USED TO ASSESS SCORE: Ophthalmoscope and fluorescent strips.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #1,#2 and #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Remarks:
- for treated eye and untreated eye
- Irritation parameter:
- iris score
- Basis:
- animal: #1,#2 and #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Remarks:
- For treated eye and untreated eye
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #1,#2 and #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Remarks:
- For treated eye and untreated eye
- Irritation parameter:
- chemosis score
- Basis:
- animal: #1,#2 and #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Remarks:
- For treated eye and untreated eye
- Irritant / corrosive response data:
- The following were observed in treated rabbits.
Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all 3 animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in Animal no. 2 and 3; Chemosis: No swelling was observed in all the 3 animals.
Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all 3 animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels were found to be normal in all the 3 animals; Chemosis: No swelling was observed in all the 3 animals.
At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 % damage in animal no. 1, 2 and 3.
Observation at 48 and 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae – Blood vessels were normal in all the animals; Chemosis: No swelling was observed in all the animals.
The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for Corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00,0.00, respectively. - Other effects:
- Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period.
Mortality
No mortality was observed during the observation period.
Body weight
All rabbits were weighed on test day 0 (prior to application) and at termination.
Any other information on results incl. tables
Table 1 : Individual Animal Eye Irritation Scores
In Treated area Dose:100 mg (0.1gm) of test item Sex:Female
Animal Numbers |
1 |
2 |
3 |
||||||||||||||||||||||||||||
Application Side |
Left |
Right |
Right |
||||||||||||||||||||||||||||
Eye Reactions |
At hour |
At hour |
At hour |
||||||||||||||||||||||||||||
* |
1 |
24 |
48 |
72 |
* |
1 |
24 |
48 |
72 |
* |
1 |
24 |
48 |
72 |
|||||||||||||||||
Corneal Opacity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||||||||||||||||
Area of Opacity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||||||||||||||||
Iris |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||||||||||||||||
Conjunctiva |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
||||||||||||||||
Chemosis |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||||||||||||||||
Corneal Damage% |
0 |
0 |
0 |
Dose:Untreated (Control Eye) Sex:Female
Animal Numbers |
1 |
2 |
3 |
||||||||||||
Application Side |
Right |
Left |
Left |
||||||||||||
Eye Reactions |
At hour |
At hour |
At hour |
||||||||||||
* |
1 |
24 |
48 |
72 |
* |
1 |
24 |
48 |
72 |
* |
1 |
24 |
48 |
72 |
|
Corneal Opacity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Area of Opacity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Iris |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Conjunctiva |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Chemosis |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Corneal Damage% |
0 |
0 |
0 |
Key:*= Pre-exposure eye examination.
Table 1 Continued…
Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Treated eye)
Animal No. Eye Reaction |
1 |
2 |
3 |
Corneal Opacity |
0.00 |
0.00 |
0.00 |
Iris |
0.00 |
0.00 |
0.00 |
Conjunctiva |
0.00 |
0.00 |
0.00 |
Chemosis |
0.00 |
0.00 |
0.00 |
Formula :
Mean Eye Irritation Score =
Sum of the Individual Animal Score for eye reactionat24, 48 and 72 hours
Number of the Observations (3)
Table 2 : Individual AnimalClinicalSigns
Sex:Female
Animal No. |
Days (Post application observation) |
|||
0 |
1 |
2 |
3 |
|
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
3 |
1 |
1 |
1 |
1 |
Key:1 = Normal
Table 3: Individual Animal Body Weight
Sex :Female
Animal No. |
Animal Body Weight (kg) |
|
Prior to application |
At termination |
|
1 |
2.362 |
2.385 |
2 |
1.746 |
1.796 |
3 |
2.136 |
2.148 |
Key:kg = Kilogram
Applicant's summary and conclusion
- Interpretation of results:
- other: not irritating
- Conclusions:
- Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed within 72 hours. Hence, test chemical is “Non Irritant” to New Zealand White Female rabbit eyes and is thus not classified as a eye irritant.
- Executive summary:
Acute eye irritation/corrosion study was conducted in rabbits to evaluate the eye irritant nature of the test chemical. The study was performed as per OECD 405 Guidelines using 3 female New Zealand White rabbits.
Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 100 mgof test itemwas instilled in the other (treated) eye of each rabbit.The eye was observed at 1, 24, 48 and 72 hour after test item instillation.Ophthalmoscope was used for scoring of eye lesions. In the initial test,100 mg of test item (Pulverized Form)was applied into the conjunctival sac of the left eye of animal no.1 whereas the right eye of the rabbit served as the control. As animal no. 1 showed no ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 100 mgof test itemwas instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. Ocular lesions were seen in animal no. 2 and 3 at 1 hour observation which recovered at 24 hour. Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test item revealed: Cornea-No ulceration or opacity in all 3 animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in Animal no. 2 and 3;Chemosis:No swelling was observed in all the 3 animals. Observation at 24 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae - Blood vessels were found to be normal in all the 3 animals;Chemosis:No swelling was observed in all the 3 animals.
At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 % damage in animal no. 1, 2 and 3. Observation at 48 and 72 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae -Blood vessels were normal in all the animals;Chemosis:No swelling was observed in all the animals. The individual mean score for animal nos. 1, 2 and 3at 24, 48, 72 hoursfor corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.00, 0.00; 0.00, 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, 0.00 respectively.
Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed within 72 hours. Hence, the test chemical is considered as “Non Irritant” to eyes of New Zealand White female rabbit eyes and thus this chemical is “Not Classified” as per CLP Regulation.
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